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The sense of smell varies depending on the person’s life history

Researchers demonstrate that the environment around the individual contributes to modulating the number of cells that identify each smell

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Smell, the sense with which odors are distinguished, is shaped by the individual's history and not just by their genetic makeup, as was previously believed. The functioning and constitution of the nose of someone exposed to a certain smell throughout their life are different from the functioning and constitution of the nose of another person who grew up and lived in another environment, with other odors. This is what a team involving 17 researchers from four laboratories specializing in the study of olfaction, distributed in three countries, discovered: the United States, England and Brazil. Among them is the group coordinated by professor Fabio Papes, from the Genomics and Expression Laboratory (LGE), from the Biology Institute (IB) at Unicamp.

The work used laboratory mice as a model and is currently being published in an article in magazine eLife, a journal in the biomedical and life sciences areas, with a high impact factor (9.0 in 2016), and which adopts a rapid editorial process, with the aim of giving visibility to the work of young professors. In the publication, the researchers detail experiments carried out at Unicamp, Duke University and Monell Chemical Senses Center (United States), and at Wellcome Trust Sanger Institute (England), coordinated by professor Darren Logan. At Unicamp, a detailed histological and molecular study of the animals' olfactory tissue was carried out, with the aim of verifying how the genes involved in the functioning of smell perception are expressed in the nasal cavity.

The olfactory tissue is composed of peripheral sensory neurons, which have molecular receptors dedicated to the detection of odor molecules. While only three types of receptors participate in the visual system and 49 types of receptors perceive different flavors in taste, in the sense of smell there are 1.200 types of olfactory receptors. Furthermore, the identification of smells occurs in a combinatorial manner, as an odor can be detected by several olfactory receptors acting simultaneously. Therefore, the repertoire of odors that humans can detect is extremely large, contributing to a practically unlimited ability to smell.

“The olfactory system is the most complex among the sensory systems, from a molecular point of view. It is also the most evolutionarily primitive, having emerged with this broad detection capacity because it is not possible to predict what types of odors we will be exposed to throughout our lives. It is different from visual or auditory information, which is comparatively much more predictable”, highlights Fabio Papes.

The unprecedented aspect demonstrated by the research is that the environment in which the individual lives and develops substantially contributes to modulating the number of cells capable of identifying each smell. "It's not about the effect that the individual's experience has on how the brain interprets sensory information, which could be considered olfactory memory, but about the actual construction of olfactory tissue." According to the professor, "the cellular and molecular construction of olfactory tissue, at a given moment, is prepared not only by the organism's genes, but also by its life history."

Olfactory neurons are formed throughout an individual's life, and the study data show that the modulation of olfaction imposed by the environment leads to the emergence of more cells capable of detecting smells to which there has been greater exposure over time. “You have more cells for that smell”, adds the professor. As a consequence, different individuals, even if genetically similar, can have completely different olfactory capabilities, which contributes to the individuality of the sense of smell, including in humans.

Photo: Antoninho Perri
Professor Fabio Papes: “The olfactory system is the most complex among the sensory systems”.

In one of the experiments, the teams implanted genetically different mouse embryos (A and B) into the same type of surrogate female, thus ensuring that the environment to which the pups were exposed during pregnancy was identical. At the end of pregnancy, pups of genetic type A were transferred to be fed by an adult female of type A, with the exception of one pup, which had a different genetic constitution B. On the other hand, the test was also conducted in the opposite way: pups of type B were fed by B females, in addition to a different offspring, of type A. "We had four groups with variations in environment and genes”, highlights Papes.

The experiments allowed researchers to compare animals that were genetically identical but grew and developed in different environments; Likewise, they were able to compare animals that grew up in the same environment but were genetically different. The olfactory organs of these animals were then evaluated using a combination of histological and molecular techniques, including sequencing of the genes expressed there. In the end, it was possible to evaluate the contributions of genes and the environment in the construction of olfactory tissue.

“It became clear that the role of genes, especially those that encode olfactory receptors in the genome, is very important in the construction of nasal tissue, but there was a very notable contribution from the environment, something never before recorded,” notes Papes.

In another experiment, the role of the environment was better evaluated. Four odors were offered to the mice over six months. The final result showed that the number of cells that have receptors for these four compounds increased almost 100 times, although genes are still largely responsible for organizing the other types of cells in the olfactory tissue.

Photo: Antoninho Perri
Professor Fabio Papes (right) with students Thiago Nakahara and Paulo Henrique Martins Netto.

 

Implications

The understanding that the construction of neurons in the olfactory tissue also depends on the individual's history may have implications for the understanding of all sensory systems, says professor Fabio Papes. “The great contribution of the study is to understand how the sense organs are not the same in all individuals. This is something with enormous medical implications, for example, as different individuals can respond to the environment in different ways, including in pathological conditions. Not because their physiologies are adapted differently, but because their sense organs per se are constructed in different ways, depending on their life story".

In a personalized medicine context, this statement could be significant. "We cannot assume that everyone has the same capacity for sensory perception and treat them in the same way”, argues the professor. In some extreme cases for certain illnesses, the loss of sensory capacity is already routinely assessed. For example, in some countries , the loss of olfactory capacity is already used to diagnose certain neurodegenerative diseases, such as Alzheimer's and Parkinson's.

Photo: Disclosure
Fluorescence image showing the olfactory organ seen from the side of the nose, with some neurons stained in red and green.

With the advancement of studies and the change in paradigm in relation to the individuality of the senses, Professor Papes highlights that it will eventually be possible to draw correlations between different sensory perception capabilities and certain medical conditions, even in less extreme situations.

Fabio Papes also highlights that the importance of the olfactory system for understanding how the brain works is reason enough to study it. “The number of areas of the brain devoted to the functioning of the olfactory system is very large, even in humans. Understanding them is a way of understanding how the brain works, how the brain processes information. It would be a way of accessing the brain, using a kind of shortcut.”

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Photo: Antoninho Perri

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